反应详情

A solution of 7-methoxy-6-methyl-1-[1-(3-thienyl)cyclopropyl]-3,4-dihydroisoquinoline (2.0 g, prepared in a similar manner to that described in Example 6) in dichloromethane (87 ml) was added slowly to an ice-cooled stirred mixture of sodium tris[(S)-N-(tert-butoxycarbonyl)prolyloxy]borohydride (11.4 g) in dichloromethane (70 ml). After standing at about 4° C. for 2 days a further portion of the reducing agent (2.0 g) was added and the mixture stirred at ambient temperature for 3 hours, then saturated aqueous oxalic acid solution (150 ml) was added. This mixture was stirred for 1 hour then basified with concentrated aqueous ammonia solution and extracted with dichloromethane (4×100 ml). The combined extracts were washed with water (100 ml) then brine (100 ml) then dried over magnesium sulphate and the solvent removed in vacuo to give a pale orange gum. The gum was dissolved in ether (150 ml) and treated with a solution of oxalic acid in ether (0.43M; 20 ml) and the resulting precipitate filtered then recrystallised from ethanol to give a single enantiomer of 7-methoxy-6-methyl-1-[1-(3-thienyl)cyclopropyl]-1,2,3,4-tetrahydroisoquinoline oxalate (1.2 g) which was used without further characterisation.

1. temperaturecooled
2. additiona further portion of the reducing agent (2.0 g) was added
3. stirringthe mixture stirred at ambient temperature for 3 hours
4. stirringThis mixture was stirred for 1 hour
5. extractionextracted with dichloromethane (4×100 ml)
6. washThe combined extracts were washed with water (100 ml)
7. dry with materialbrine (100 ml) then dried over magnesium sulphate
8. customthe solvent removed in vacuo
9. customto give a pale orange gum
10. filtrationthe resulting precipitate filtered
11. customthen recrystallised from ethanol